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Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.

Sutton ME, op den Dries S, Karimian N, Weeder PD, de Boer MT, Wiersema-Buist J, Gouw AS, Leuvenink HG, Lisman T, Porte RJ - PLoS ONE (2014)

Bottom Line: Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group.Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group.It could potentially be used to identify extended criteria livers that are suitable for transplantation.

View Article: PubMed Central - PubMed

Affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

ABSTRACT
Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37 °C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥ 30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.

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Histology of livers after 6 hours of normothermic machine perfusion.In comparison to livers with high bile output, livers in the low bile output group displayed more signs of hepatic necrosis (panels A and B) and venous congestion (panels C en D). Despite these differences in hepatic parenchymal damage between the two groups, there were no major differences in the degree of biliary damage (panels E and F).
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pone-0110642-g004: Histology of livers after 6 hours of normothermic machine perfusion.In comparison to livers with high bile output, livers in the low bile output group displayed more signs of hepatic necrosis (panels A and B) and venous congestion (panels C en D). Despite these differences in hepatic parenchymal damage between the two groups, there were no major differences in the degree of biliary damage (panels E and F).

Mentions: Finally, we compared histology of liver grafts after 6 h of NMP between the two groups. In accordance with the observed differences in biochemical markers of hepatic injury, livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group (Figure 4 A-D). Venous congestion was present in 5 out of 6 livers (83%) in the low bile output group and in 2 out of 6 livers (33%) in the high bile output group (p = 0.08). Necrosis >30% was observed in 4/6 (66%) of the livers in the low bile output group and in 2/6 (33%) livers in the high bile output group (p = 0.25). Despite these differences in hepatic parenchymal damage between the two groups, there were no major differences in the degree of biliary damage (Figure 4 E-F).


Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion.

Sutton ME, op den Dries S, Karimian N, Weeder PD, de Boer MT, Wiersema-Buist J, Gouw AS, Leuvenink HG, Lisman T, Porte RJ - PLoS ONE (2014)

Histology of livers after 6 hours of normothermic machine perfusion.In comparison to livers with high bile output, livers in the low bile output group displayed more signs of hepatic necrosis (panels A and B) and venous congestion (panels C en D). Despite these differences in hepatic parenchymal damage between the two groups, there were no major differences in the degree of biliary damage (panels E and F).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219693&req=5

pone-0110642-g004: Histology of livers after 6 hours of normothermic machine perfusion.In comparison to livers with high bile output, livers in the low bile output group displayed more signs of hepatic necrosis (panels A and B) and venous congestion (panels C en D). Despite these differences in hepatic parenchymal damage between the two groups, there were no major differences in the degree of biliary damage (panels E and F).
Mentions: Finally, we compared histology of liver grafts after 6 h of NMP between the two groups. In accordance with the observed differences in biochemical markers of hepatic injury, livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group (Figure 4 A-D). Venous congestion was present in 5 out of 6 livers (83%) in the low bile output group and in 2 out of 6 livers (33%) in the high bile output group (p = 0.08). Necrosis >30% was observed in 4/6 (66%) of the livers in the low bile output group and in 2/6 (33%) livers in the high bile output group (p = 0.25). Despite these differences in hepatic parenchymal damage between the two groups, there were no major differences in the degree of biliary damage (Figure 4 E-F).

Bottom Line: Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group.Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group.It could potentially be used to identify extended criteria livers that are suitable for transplantation.

View Article: PubMed Central - PubMed

Affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

ABSTRACT
Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37 °C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥ 30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.

Show MeSH
Related in: MedlinePlus